Role of periostin expressing cells in intramembranous bone regeneration

骨膜蛋白表达细胞在膜内骨再生中的作用

• 批准号: 10440350
• 负责人: Frank Ko
• 金额: $ 11.95万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10440350
• 关键词: Ablation; Academic Medical Centers; Address; Advisory Committees; Allografting; Animals; Award; Biological Assay; Biomechanics; Biometry; Bone Marrow; Bone Marrow Ablation; Bone Regeneration; Cell Culture Techniques; Cells; Committee Members; Complement; Core Facility; Data; Development Plans; Distraction Osteogenesis; Event; Failure; Femur; Gene Expression; Genes; Goals; Grant; Histology; Immunohistochemistry; Impairment; Implant; In Vitro; Injury; Institution; Knock-out; Knowledge; Label; Lead; Light; Marrow; Mediating; Mentors; Microscopy; Modeling; Molecular; Molecular Biology; Molecular Medicine; Molecular Profiling; Mus; Natural regeneration; Operative Surgical Procedures; Orthopedic Procedures; Orthopedic Surgery; Orthopedics; Osteoblasts; Pathway interactions; Patient Care; Patients; Periosteum; Phenotype; Play; Procedures; Process; Publications; Recovery; Regenerative pathway; Replacement Arthroplasty; Reporter; Research; Research Personnel; Research Training; Rodent Model; Role; Science; Scientist; Series; Skeletal Development; Technical Expertise; Therapeutic; Time; Tissues; Training; Up-Regulation; Vocational Guidance; Writing; base; bone; bone fracture repair; bone mass; bone repair; care providers; career development; experience; implantation; improved; insight; intramembranous bone; lectures; microCT; novel; novel therapeutics; osteogenic; periostin; professor; protein expression; research and development; responsible research conduct; sample fixation; skeletal disorder; skeletal stem cell; spatiotemporal; stem cell biology; stem cells; substantia spongiosa; tissue regeneration; tomography

Project Summary/Abstract: The proposal includes a comprehensive 5-year mentored career development plan for Dr. Frank Ko to transition to an independent investigator who studies intramembranous bone regeneration. The candidate is currently an assistant professor in the Department of Cell & Molecular Medicine (CMM) at Rush University Medical Center (RUMC) and conducts his research at RUMC and at its affiliated centers and institutions. He is well supported by the institution and will devote 100% of his time to his research and career development plan. The candidate has assembled mentors and a scientific advisory committee with a wide array of complementary expertise and extensive mentoring experience to offer career guidance during his transition to independent research and train him in new intellectual and technical skills for his proposed studies. His mentor, Dr. Rick Sumner, is an expert in the field of bone regeneration and implant fixation, the Chair of CMM at RUMC, and the director of Rush MicroCT/Histology Core Facility. His co-mentor, Dr. Anna Spagnoli, is a clinician-scientist with an expertise in the field of skeletal development and diseases and is the director of Section of Molecular Medicine in the Department of Orthopedic Surgery at RUMC. Scientific advisory committee member Dr. Noriaki Ono is a molecular biologist studying skeletal stem and progenitor cells. The science focuses on the role of periostin-expressing cells in intramembranous bone regeneration following marrow ablation surgery. The candidate discovered that these cells, which are normally absent in marrow and reside in the periosteum, are present in the regenerating marrow cavity following the surgery and their depletion delays intramembranous bone regeneration. Thus, the specific aims are to investigate: 1) the necessity of periostin-expressing cells and periostin in intramembranous bone regeneration; and 2) the lineage commitment, molecular signatures, and differentiation of periostin-expressing cells and their progeny during intramembranous bone regeneration. To complement his prior training in bone biomechanics and molecular biology in intact tissues, the candidate will be trained in the use of reporter mice, animal surgery, and regenerated bone phenotyping, including light sheet and expansion microscopy, gene and protein expression analyses, and in vitro culture and assay. Further, he will participate in career development activities that include didactic lectures and seminar series focusing on tissue regeneration, stem cell biology, biostatistics, grant writing, responsible conduct of research, and scientific presentation. This K01 proposal will allow the candidate to gain valuable career development mentoring to achieve his goal of becoming an independent investigator studying intramembranous bone regeneration.

项目摘要/摘要：该提案包括全面的 5 年指导职业发展 计划让 Frank Ko 博士转型为研究膜内骨的独立研究者 再生。该候选人现为细胞与分子医学系助理教授 拉什大学医学中心 (RUMC) 的 CMM，并在 RUMC 及其附属机构进行研究 中心和机构。他得到了机构的大力支持，并将投入100%的时间进行研究 和职业发展计划。候选人召集了导师和科学顾问委员会 广泛的互补专业知识和丰富的指导经验，可在期间提供职业指导 他向独立研究的过渡，并为他的提议培训他新的知识和技术技能 研究。他的导师 Rick Sumner 博士是骨再生和种植体固定领域的专家， RUMC CMM 主席，Rush MicroCT/组织学核心设施主任。他的共同导师安娜博士 Spagnoli 是一位临床医生兼科学家，在骨骼发育和疾病领域拥有丰富的专业知识， RUMC骨科分子医学科主任。科学的 顾问委员会成员 Noriaki Ono 博士是一位研究骨骼干和祖细胞的分子生物学家 细胞。该科学重点关注表达骨膜素的细胞在膜内骨再生中的作用 骨髓消融手术后。候选人发现这些细胞通常不存在于 骨髓并驻留在骨膜中，手术后存在于再生骨髓腔中， 它们的消耗会延迟膜内骨的再生。因此，具体目标是研究：1） 表达骨膜素的细胞和骨膜素在膜内骨再生中的必要性； 2）血统 表达骨膜素的细胞及其后代的承诺、分子特征和分化 膜内骨再生。为了补充他之前在骨生物力学和分子学方面的培训 完整组织生物学，候选人将接受使用报告小鼠、动物手术和 再生骨表型分析，包括光片和扩展显微镜、基因和蛋白质表达 分析以及体外培养和测定。此外，他还将参加职业发展活动 包括侧重于组织再生、干细胞生物学、生物统计学的教学讲座和研讨会系列， 拨款写作、负责任的研究行为和科学演示。该 K01 提案将允许 候选人获得宝贵的职业发展指导，以实现成为独立人士的目标 研究膜内骨再生的研究者。